Enhancing Metalating Efficiency of the Sodium Amide NaTMP in Arene Borylation Applications

Abstract

Though LiTMP (TMP=2,2′,6,6′‐tetramethylpiperidide) is a commonly used amide, surprisingly the heavier NaTMP has hardly been utilised. Here, by mixing NaTMP with tridentate donor PMDETA (N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine), we provide structural, and mechanistic insights into the sodiation of non‐activated arenes (e.g. anisole and benzene). While these reactions are low yielding, adding B(OiPr)3 has a profound effect, not only by intercepting the CAr‐Na bond, but also by driving the metalation reaction towards quantitative formation of more stabilized sodium aryl boronates. Demonstrating its metalating power, regioselective C2‐metalation/borylation of naphthalene has been accomplished contrasting with single‐metal based protocols which are unselective and low yielding. Extension to other arenes allows for in situ generation of aryl boronates which can then directly engage in Suzuki–Miyaura couplings, furnishing a range of biaryls in a selective and efficient manner.

Alkali-metal bases in catalytic hydrogen isotope exchange processes

“…Despite all these advances, the detailed study of the reaction mechanism is still lacking in some of these transformations. DFT calculations and key mechanistic experiments have been performed in a few examples, 13,16,18,21,23,27,28,30 but in general the specific mechanistic details of these processes are still poorly understood. We predict that further developments on the use of alkali-metal bases for HIE processes will keep appearing, which in combination with a deeper mechanistic understanding will bring the use of alkali-metal bases as an excellent pathway for the incorporation of deuterium and tritium into organic molecules, with the benefits of using widely available and cheap alkali-metal reagents.…”

“…Mechanistic investigations revealed that under stoichiometric conditions using C 6 H 6 or hexane as a solvent the starting materials are in equilibrium with the relevant sodium aryl and the amine TMP(H). 27 Further evidence on the metalating ability of NaTMP to deprotonate anisole and benzene was obtained by the isolation and structural identification of the organometallic species involved in these reactions (Fig. 8b) which can be envisaged as co-complexes between the metalation products NaAr (Ar = C 6 H 4 –OMe, C 6 H 5 ) and the sodium amide NaTMP·L (L = TMEDA, N , N , N ′, N ′-tetramethylethylenediamine).…”

“…Two different structural motifs were uncovered depending on the substrate employed, containing either two or three Na centers. 26,27 The use of the NaTMP/PMDETA combination for the perdeuteration of aromatic molecules could be extended to other less reactive substrates, such as phenyl trimethyl silane, diphenyl acetylene or naphthalene (Fig. 9a), achieving high deuterium incorporations with relatively mild conditions (room temperature and a reaction time of twelve hours).…”

“…Two different structural motifs were uncovered depending on the substrate employed, containing either two or three Na centers. 26,27…”

The Versatile and Strategic O-Carbamate Directed Metalation Group in the Synthesis of Aromatic Molecules: An Update

“…However, these reagents are highly reactive and tend to attack electrophilic DMGs or sensitive functional groups, causing undesired side reactions . Subsequent research to establish alternative, less harsh metalation reagents has been fruitful, with the discovery of metalation reagents in the form of single metals (Na), sodium and metal amides, ,− sodium isopropyl­(trimethylsilyl)­amide, NaTMP (TMP = 2,2′,6,6′-tetramethylpiperidine) with tridentate donor PMDTA ( N , N , N ′, N ″, N ″-pentamethyldiethylenetriamine), mixed metals, , metalates (magnesiates, zincates, and aluminates), − (2,2,6,6-tetramethylpiperidino)magnesium chloride (TMPMgCl), mixed aggregates, , “superbases,” and “Turbo bases”. , There are only a few examples which have been demonstrated for ArOAms, shown in Table .…”